This PPT contains metabolism of Macro & Micro minerals according to competencies defined for MBBS. Students of other health Sciences can use this powerpoint presntation.

1. Smita Pakhmode
Lec-1
MINERAL METABOLISM
Dr. Smita Pakhmode,
Associate Professor
Department of Biochemistry
NKPSalve Medical College &RC

2. Smita Pakhmode
Competencies
No Competency Domain level Core Method
BI 6.9 Describe the
functions of various
minerals in the
body, their
metabolism and
homeostasis.
K KH Y Lecture,
Small
group
discussion
BI 6.10 Enumerate and
describe the
disorders
associated with
mineral
metabolism.
K KH Y Lecture,
Small
group
discussion

3. Smita Pakhmode
Biomedical
Importance of
MINERALS
Calcification of
teeth & Bone
Blood coagulation
factors
Neuromuscular
activation
Acid base
equilibrium
Osmotic
equilibrium
Acts with enzyme
( Metalloenzyme,Cofactor)
Integral part of
compounds
(Hb,Thyroxin,Insulin,
Vit B12)

4. Smita Pakhmode
Classification
Minerals
Principle
60-80%
> 100mg/day
Ca,P,Na,K,Mg,Cl,S,
TRACE ELEMENTS
<100mg/day
Essential
Fe,Cu,I,Mn,Zn,Mb,
Co,Fl & Se
Possibly Essential
Cr,Ni, Va,Cd, Barium
Non essential
Al.Pb,Hg,Boron,
Silver Bismuth

5. Smita Pakhmode
• Introduction & Classification of minerals,
• Calcium:
• Functions,
• Sources, & RDA,
• Factors affecting absorption
• Calcium Homeostasis
• Disease Manifestations of Calcium metabolism
• Phosphorus
• Functions,
• Sources, & RDA,
• Factors affecting absorption
• Disease Manifestations of phosphorus metabolism
Learning Objectives

6. Smita Pakhmode
Frequently asked questions(MBBS)
• Factors involved in the regulation of blood calcium levels.
(4M)
• Biochemical functions of calcium. (4M)
• Regulation of serum Calcium(4M)
• Functions and deficiency manifestation of Calcium. (4M)
• Hormones regulating serum Calcium.(4M)
• LAQ: Write in detail about the factors influencing calcium
absorption in the body. Write its function (8M)
• Case study: Tetany

7. Smita Pakhmode
CALCIUM
Total content : 1-1.5 Kg
99% Bones & Teeth
01% Miscible “Ca” pool ( ECF)

8. Smita Pakhmode
Functions of Calcium
1. Bone & teeth calcification
• Hydroxyapatite crystals
• Bones :Reservoir of Ca
• Regulators: Osteoblasts and PTH
2.Blood coagulation factors
• Activator of factor IV
• EDTA: Chelates Ca Anticoagulant
4.Nerve conduction
Releases neurotransmitters at presynaptic & post synaptic terminals
3.Secondary messenger: Glucagon & Epinephrine
Tertiary messenger with Cy AMP: ADH

9. Smita Pakhmode
Functions of
Calcium
6 Muscle contraction
Interaction of Ca & Troponin C
Activation of ATPase
↑Actin Myosin Interaction
Facilitate excitation contraction coupling
5.Activation of enzyme
• Calmodulin mediated
• Direct Action
Ca2+ + Calmodulin
Ca-Calmodulin Complex
Kinase. Active Kinase
Enzyme. P-Enzymes
Biological effects
Enzymes activated with Calmodulin
Adenylate cyclase, PL C
Ca dependent Protein Kinase
Gly synthase, Phosphorylase Kinase,
G3PDH, Py. Carboxylase, PDH,
Myosin kinase
Directly Activated Enzyme
Pancreatic Lipase
Coagulation enzymes
Rennin
Deficiency of Ca: Tetany

10. Smita Pakhmode
Functions of Calcium
7.Release of hormones from endocrine glands-
insulin, PTH, calcitonin
8. Myocardium: Prolongs Cardiac systole ( Caution: IV administration of
Ca. Gluconate)
10.Contact Inhibition: maintains Cell to cell adhesion
9. Secretory Process: Microtubule & microfilament
mediated functions- endocytosis, exocytosis and cell
motility

11. Smita Pakhmode
Adults 800 mg
Preg. /Lact .: 1500 mg
Growing children 800-1200 mg
DAILY REQUIREMENTS
Sources
Rich: Milk & Milk products
Medium: Egg, Fish Vegetable, Beans, Leafy vegs.
Poor but major: cereals.

12. Smita Pakhmode
FACTORS AFFECTING ABSORPTION OF CALCIUM
• Its an Active process.
• Occurs in first and & Second part of duodenum.
• Carrier protein helped by Calcium dependent ATPase
↑↑Ca absorption
Calcitriol (Active form Of Vit D)
Parathyroid hormone → ↑Vit D synthesis
Acidity/Low pH
lactose
Lysine, arginine
High protein Intake

13. Smita Pakhmode
Factors decreasing Ca absorption:
• Phytates, oxalates
• High PO4 content
Ideal Ca : P Ratio
1:2 - 2:1
• Impaired fat abs:
free fatty acids +calcium---calcium soaps
• High pH(ALKALINE PH)
• High fiber
FACTORS AFFECTING ABSORPTION OF CALCIUM

14. Smita Pakhmode
PLASMA CALCIUM
50%
10%
40%
BLOOD CALCIUM
Ionized
Anion bound
protein
bound
(5 mg/dl )
(1mg/dl)
4mg/dl.
DIFFUSIBLE
NONDIFFUSIBLE

15. Smita Pakhmode
Homeostasis of Calcium
Factors which regulate Ca levels in blood
1Hormones: 1.Calcitriol
2.Parathyroid hormone
3.Calcitonin
2.Concentration of phosphorus:
reciprocal relationship
Ionic product of ( Cal X Po4= 40)
Renal insufficiency: Excretion of Ca leads to tetany
3.Serum proteins:
Hypoalbunemia (1gm/dl)⍺ ↓Ser. Cal (0.8mg/dl)
- levels of ionized form is normal.
4.Alkalosis and acidosis: Alkalosis favors binding of calcium with proteins
Acidosis favors ionization

16. Smita Pakhmode
Blood Calcium
N level: 9-11mg/dl
Role of Vit D ( Calcitriol)
Intestine
Bone
Kidneys
Induces synthesis of
“Calcium Binding Protein”[CBP]
↓
• ↑ intestinal abs. of Ca & P (in
intestinal cells)
Stimulates osteoblasts
↑ ALP (↑ Phosphate level)
Promotes calcification of bones ↑ Reabsorption of
Calcium & phosp from
renal tubules
Increases Calcium Level
With PTH: Stimulates osteoclasts
Mobilizes Ca & Po4 from bone

17. Smita Pakhmode
Low Blood Calcium
Role of Parathyroid
hormone
Intestine
Bone
Kidneys
PTH: Stimulates osteoclasts
↑ Prophosphatase. Lactate. Collagenase
Reabsorption & solublization of bone matrix
Mobilizes Ca & Po4 from bone
↑ hydroxylation of Vit D
to form Calcitriol
↑ Ca2+
Reabsorption (
rapid action )
↓ excretion of Ca from
renal tubule
↑ excretion of Po4
Induces synthesis of
“Calcium Binding Protein”[CBP]
↓
• ↑ intestinal abs. of Ca & P (in
intestinal cells)
Vit D
Increases Calcium Level
Negative feed back regulation
Action last for 1 hour

18. Smita Pakhmode
Raised Blood Calcium
Gastrin, Glucagon &
Biological amine
Role of Calcitonin
Bone
Kidneys
↑ osteoblasts ↓ osteoclast
Inhibit reabsorption of bones
↓ blood calcium level
↑ excretion of Po4
-
decreases Calcium Level
Antagonist to PTH
Significance of Calcitonin
Tumor Marker
1) Medullary Ca of Thyroid
2) Lung & Bronchus Malignancies

19. Smita Pakhmode
TEETH CALCIUM NOT SUBJECT TO REGULATION
When to check Calcium levels??
 Neurological symptoms, irritability
 Urinary Calculi
 Ectopic Calcification
 Suspected Malignancies
 Polyurea, Polydypsis
 Chronic Renal failure
 Prolong treatment with drugs which cause Hypercalcemia (
Vit D, Thiazide Diuretics)

20. Smita Pakhmode
DISORDERS OF CALCIUM METABOLISM
• Hypercalcemia :
Etiology:
1. Hyperparathyroidism ( Adenoma/ Ectopic PTH
tumor)
2. Multiple Myeloma, Paget’s disease, Metastatic Ca
3. thyrotoxicosis, Addison's disease,
4. Prolong Immobilization
5. TB, Leprosy & Sacrcoidosis
6.Drugs: Thiazide, Vit D, IV calcium, Lithium Therapy

21. Smita Pakhmode
DISORDERS OF CALCIUM METABOLISM
• Hypercalcemia :
Effects: Serum ↑Ca , ↓PO4
Urine ↑Ca , ↑PO4
Ionized serum Ca ↑(6-9mg/dl),
Raised Alkaline phosphatase
urinary calculi & osteoporosis
s/s– Polyurea, polydipsia, confusion, depression , psychosis,
Pathological fracture, renal stone, ectopic calcification &
Pancreatitis
T/t: Adequate hydration, IV frusemide, Steroids.
T/t of underlaying cause.

22. Smita Pakhmode
• Hypocalcaemia( < 8.8mg/dl)
mostly due to hypo PTH
Other Causes:
1. Deficiency of Vit D
2. Medullary Ca of Thyroid (↑ Calcitonin)
3. Malabsorption disorders, Acute Pancreatitis,
Alkalosis(↓Ca )
4. Renal failure, RTA, Phosphate infusion (↑PO4)
S/S: Muscle cramps, paresthesia, neuromuscular
irritability, muscle twitching,
Accidental removal
Autoimmune
DISORDERS OF CALCIUM METABOLISM

23. Smita Pakhmode
Mild deficiency of Calcium
Chronic Ca deficiency Cause:
Dietary deficiency of Vit D or Ca
Renal insufficiency
Mg deficiency
White patches on nails
Deformities of weight bearing bones
Treatment:
Oral Ca & Vit D
supplementation
T/t of underlying
cause

24. Smita Pakhmode
• TETANY (<7.5 mg/dl)
• Serious life threatening disorder
S/o: neuromuscular irritability, Spasm & convulsions
• mostly due to accidental or autoimmune removal of Parathyroid
Gland
• Dignostic signs
TETANY (<7.5 mg/dl)
Serum ↓Ca , ↑PO4
Urine ↓Ca , ↓ PO4
T/t—Severe cases—IV Ca Gluconate
(10ml of 10% Calcium glucaonate over 10 min)
Imp Note: VIT D Deficiency will never cause Tetany
Severe Calcium deficiency: TETANY

25. Smita Pakhmode
Carpopedal Spasm:
Flexion of wrist
Flexion MPJ &
Extension IP joints
Adduction of thumbs & fingers
Trousseu’s sign: Inflation of BP cuff for 3 min
will cause carpopedal spasm
Chvostek’s Sign: Tapping over facial
muscle causes facial muscle
contraction
Other Signs:
Laryngeal stridor,
Prolong QT interval
Signs of Tetany

26. Smita Pakhmode
Relationship of Calcium & Phosphorus
• RDA
Ratio of 1:1 Ca : P ( i.e. 800 mg /day)
• Diet:
• optimum Ca: P ratio 1:2 - 2:1
• Favors absorption
• Blood:
• Ionic product of CaXP (10X4)= 40
• Ratio is important for the calcification of Bone
• High Ratio: mineralization of Bones
Children- 50
• Low ratio: Ricket (<30)

27. Smita Pakhmode
Case
• A 54 years years old grossly overweight women presented
with the complaints of cramps and spasms of both hands. She
was depressed and positive Trasseau’s sign & Chovestek’s
sign. Past medical history reveals thyroidectomy for Grave’s
disease. The laboratory findings are as follows:
Serum Ca: 4.1 mg%; Sr. Creat: 1.0mg%, Sr. Po4 :5.9mg%; Sr
Alb:4.0mg%
• What is the diagnosis?
Tetany
What is probable cause for the disease?
Hypoparathyroidism due to removal of PTH glands
• Interpret laboratory finding and corelate with diagnosis ?
hypocalcemia& Hyperphosphatemia with N Creat & Alb
• What additional test to be done for conclusive diagnosis?
• Estimation serum PTH level & Alk Po4 level. Low PTH & High ALP

28. Smita Pakhmode
Case
• A 10 year old boy presented with the complaints of muscle pain ,
stiffness ,cramps of both hands & feet. He was strict vegetarian &
even did not consume milk & dairy products. On examination no
signs of rickets were found. He had positive Trousseau’s sign &
Chovestek’s sign. Serum Calcium level is as low as 4mg%.
• What is the diagnosis?
• Tetany
• What is probable cause for the disease?
• Hypoparathyroidism Or Chronic renal Failure
• How would you investigate the case to confirm diagnosis ?
• KFT( Urea, Creat,Electrolyte & Urinary Ca & Po4 ratio: CRF
• Estimation serum PTH level & Alk Po4 level: Low PTH & High ALP
• Estimation of Vit D

29. Smita Pakhmode
Case
• A 42 year old lady presented with the complaints of vague
abdominal discomfort, fatigue & bone pain. She had frequent
episodes of urinary track infection and episodes of urinary
stone. Her physical examination was within normal limits.On
investigations patient had N CBC, Electrolyte: High Ca & low
Po4.
• What is the diagnosis?
• HyperCalcemia & Hypophosphatemia :Hyperparathyroidism
• What is probable cause for the disease?
• Primary Hyperparathyroidism(stone,moans,groans,bones)
• How would you investigate the case to confirm diagnosis ?
• Estimation serum PTH level
• Estimation of Vit D

30. Smita Pakhmode
PHOSPHORUS
Total Body content = 1 Kg
80% Bones & teeth
10% Muscles , blood
10% chemical compounds
Functions
1. Bones and teeth
2. High energy compounds ( ATP , GTP, Cr-P )
3. Phospholipids, Phosphoproteins, Nucleic acids(DNA/
RNA)
4. Nucleoside Coenzymes NAD+ , NADP+ ,Pyridoxal PO4
5. Activation of Proteins and enzymes by phosphorylation
6. Phosphate buffers system( Na2HPO4/NaH2Po4 =4:1)
7. Formation of phosphate esters. G 6 P,PL, phosphoprotein

31. Smita Pakhmode
Absorption
Absorption in jejunum
↑by - Calcitriol
- optimum Ca: P ratio 1:2 - 2:1
- Acidity
↓by Phytates ( cereal rickets )
RDA : Ratio of 1:1 Ca : P ( i.e. 800 mg /day)
Infants 2:1 ( Milk )
Sources
Milk , eggs, meat, fish ,cereals, leafy vegetables,
cheese, beans,
PHOSPHORUS

32. Smita Pakhmode
Factors Regulating Phosphorus in Blood:
Vit D & PTH
Excretion:
500 mg / day in urine
Renal threshold → 2 mg /dl
PTH → Inhibits reabsorption of PO4 by RT
Conc. In Blood:
Serum Level: Total 3-4 mg / dl
Whole blood - 40 mg /dl ( ↑content RBC, WBC’s)
Fasting > Post meal
Distribution:
40% free ions
10% protein bound
50% bound to cations
(Ca2+
/ Mg2+
/ Na+ /K+ )

33. Smita Pakhmode
Disorders of phosphate
Hyperphosphatemia:
↑ absorption of the phosphate:
↑ Vit D/ Po4 infusion
↑ Cell lysis:
Cancer chemotherapy, Bone secondaries,
↓ excretion :
Renal Impairment, Hypoparathyroidism,
Acidosis
Drugs:
Chlorthiazide, Nifedipine, Frusemide

34. Smita Pakhmode
Disorders of phosphate
• Hypophosphatemia:
• ↓ absorption of the phosphate:
• Malnutrition, Malabsorption, Chr. Diarrhea, Vit D
deficiency.
• Intracellular shift: Insulin therapy, Renal rickets
• ↑ urinary excretion of phosphate:
Hyper parathyroid hormone, hypophosphatemic
rickets.
Hypercalcemia, Chronic alcoholism, Drugs
• Drugs: Antacids, Diuretics, salicyclate

35. Smita Pakhmode
RDA Males – 350 mg/day
Females – 300 mg/day
Sources Cereals, nuts, beans, vegetables { cabbage, cauliflower}, meat,
milk & fruits
Magnesium (Macroelement)
Total content in the body : 20 g
70 % bones & teeth
30% soft tissue & body fluids
Absorption Upto 50% ( carrier mediated )
↑↑ by PTH
Ca , P, Alcohol - ↓Mg Absoption
Excretion Mostly → Intestine
Partly→ Kidneys
Serum levels Total 2-3 mg / dl
60% - Ionised
10% - bound to anions
30% - Protein bound

36. Smita Pakhmode
Functions
• Bone and teeth
• Cofactor for ATP requiring enzymes
• e.g. hexokinase , PF kinase , glucokinase, adenylate cyclase
• Neuromuscular functions
• Improves glucose tolerance .
• Reduces BP & prevents stroke
• Clinical applications:
• When given in large doses (parenterally )
• CNS depressant
• (Hence anesthetic / anticonvulsant )

37. Smita Pakhmode
Disorders:
Hypomagnesemia( low serum Mg ):
•Renal tubular necrosis, Liver Cirrhosis, Toxemia of
pregnancy ,Malnutrition ,
C/F – Neuromuscular irritability
weakness
convulsions
Magnesium Toxicity :
Magnesium containing Antacids/ Laxatives
C/F - Drowsiness
Lethargy
Weakness

38. Smita Pakhmode
Sulphur
Most important component of body proteins.
Sources: S – AA
Vegetable & Cereals
No specific RDA
Excretion: 1gm/day through urine
1. Inorganic sulphate
2. Ethereal sulphate
3. Unoxidized sulphate

39. Smita Pakhmode
Functions of Sulphur
1. Mitochondrial cellular respiration
Component of Fe-S Containing protein
2.Stabilize the protein structure: Insulin, Immunoglobulins
3. Part of different coenzyme:
Thiamine, Biotin, Lipoic Acid, Coenzyme A
4. Part of fibrous proteins:
Keratin of hair & Nail
5.Part of different metabolically active compounds:
Glutathione, heparin, Chondrotin Sulphate,
taurocholic acid
6. Detoxification reactions:
Phosphoadenosine Phosphosulphate (PAPS)
7. Transmethylation Reaction:
S- Adenosine Methionine

40. Smita Pakhmode
Sodium
Major CATION in ECF
70%- ECF
4-5%-ICF
20%-soft tissues, bone teeth
Requirement: 5-10 gm/day as NaCl
Source :
Common Salt
Cereals, legumes, leafy vegetables, nuts, eggs, milk
Absorption : 99% in GIT

41. Smita Pakhmode
Functions of Sodium:
1. Maintains ECF volume
2. Osmotic pressure & fluid balance
3. Acid-base balance:
4. Component of Na K pump
5. Absorption of glucose, galactose, amino acids
6. Nerve muscle conduction.

42. Smita Pakhmode
Distribution of Na in body
4000meq
75%
Exchangable
ECF
70%
ICF
4%
25% Non
Exchangable
Bone, teeth
& soft tissue
Normal level = 135-145 meq/L-ECF
35 meq/L-ICF

43. Smita Pakhmode
Regulation of Sodium
Decrease in BP
Rennin
Angiotensinogen1
Angiotensin1
Angiotensin II
AngiotensinII
Aldosteron
Na+ Retention
Excretion of K+ & H+
ANF Aldosterone system
↑ BP
↑GFR……..
↑Na+ excretion
↑Urine out put
↓ in Na Conc

44. Smita Pakhmode
Factors affecting serum Sodium levels:
Aldosterone : ↑↑ Na + reabsorption
ADH : ↑↑ water reabsorption
Edema: ↑ water, Na+ content
Diuretics: → ↑Na+ excretion, water
excretion
Excretion: by Kidneys & sweating
800 gm/day Na+ filtered
99% of this is Reabsorbed
Na Homeostasis

45. Smita Pakhmode
Hyponatremia
Method of Estimation: Flame photometry /Ion selective
electrode
Symptoms: Muscle cramps, Headache & Nausea
Long term complication Sign: B.P.& Circulatory Failure, Edema

46. Smita Pakhmode
Causes of Hyponatremia
Hyponatremia
↓osmolality
Hypervolemia
CCF, Cirrhosis,
Nephrotic Syndrome
Euvolemia
SIADH
Pneumonia,
Pulm. TB, Ca
Bronchus
Hypovolemia
Extra renal
Diarrhoea,
vomiting
Sever
Sweating
Renal
↓ADH, Aldosteron
(addisons disease)
RTA
Diuretcs

47. Smita Pakhmode
Hypernatremia
Hypernatremia
Blood volume
Hypervolemic
Cushing’s Syndrome
Prolong steroid
therapy
Pregnancy
Excess of
Mineralocorticoid
Euvolemic
Diabetes Insipidus
Hypovolemic
Dehydration
Diarrhoea,
vomiting
With reduced
fluid intake
Diuretics

48. Smita Pakhmode
POTASSIUM
Major intracellular cation
Total Body content: 3500 meq
75% in muscles & ICF
RDA : 3-4 gm/day
Sources : Bananas, oranges, apples, almonds, dates, beans,
potatoes, coconut water, beans , chicken and liver
Normal level = 3.5-5meq/L (ECF)
50meq/L (ICF)
Daily Intake: 20-200 meq/ Day
Excretion: Urine
Aldosterone: ↑ excretion of K+

49. Smita Pakhmode
Functions
•Intracellular osmotic pressure & volume.
•Component of Na K pump
•Acid-base & Water balance
•Imp in depolarization & contraction of cardiac muscles
•Nerve impulse transmission
•Enzyme Pyruvate Kinase Activity
•Protein Biosynthesis

50. Smita Pakhmode
Regulation of Potassium
Serum K
Redistribution
Of K
Insulin Acidosis
Increased
Excretion
↑Aldosterone
↑Corticosteroid

51. Smita Pakhmode
HYPOKALEMIA
(<3 meq/L)
Symptoms:
Vomiting, Diarrhea, Weakness, Anorexia
Irritability, Muscle weakness, Arrhythmias, Cardiac arrest,
ECG changes:
Flattened /lowering/ inversion of T wave
ST seg depression, prominent U wave
Arrythmia

52. Smita Pakhmode
Hypokalemia
Hypokalemia
Redistribution
Of K
Insulin therapy
T/t Aciodocis
Meta. Alkalosis
Catecholamine
B adrenergic drugs
Periodic Paralysis
True loss of K
through Urine
K Excretion> 25
Meq/Day
RTA
A TN
↑Aldosterone
↑Corticosteroid
K Excretion < 25
meq/Day
Diarrhoea
Fistula
Extensive surgery

53. Smita Pakhmode
Hyperkalemia
Hyperkalemia
Pseudo
Hemolysis
Thrombocytosis
Redistribution
Of K
Insulin Deficiency
Meta Acidosis
K Retention
Massive Blood
transfusion
Renal transplant
Obstructive
nephropathy
Addison's Disease
SLE/ SCD

54. Smita Pakhmode
HYPERKALEMIA: (> 5.5 meq/L)
Symptoms: s/o depression of CNS
Weakness, decreased Deep tendon reflexes
numbness bradycardia , Cardiac arrest.
ECG changes:
prominent T wave
widening of QRS complex
Prolong PR interval

55. Smita Pakhmode
Lec-2
MINERAL METABOLISM
Dr. Smita Pakhmode,
Associate Professor
Department of Biochemistry
NKPSalve Medical College &RC

56. Smita Pakhmode
Commonly asked questions(MBBS)
• Absorption & function of iron.(4M)
• Mechanism of iron absorption from the intestine. (4M)
• Write a note on intestinal absorption of Iron. (4M)
• Factors affecting intestinal absorption of Iron. (4M)
• Case on Iron deficiency Anemia (4M)
• Explain the defect in Wilson’s disease, state the clinical
manifestations (4M)
• Functions of Copper(4M)
• Case on Wilson’s Disease.(4M)

57. Smita Pakhmode
IRON:
• Functions,
• Sources, & RDA,
• Factors affecting absorption of iron
• Regulation of Absorption of Iron
• Disease Manifestations of Iron metabolism
• Copper
• Distribution & Functions,
• Sources, & RDA,
• Biochemical functions
• Disease Manifestations
Learning Objectives

58. Smita Pakhmode
IRON
3-5gm
•
• Requirements-
Daily allowance (ICMR)
Adult man: -10mg /day
Mensturating women: 18mg/day
Pregnancy/Lactation- 40mg/day
Children (13-15yrs)-30mg/day
75% -blood
20% - liver, bone marrow
5%muscles
Absorption: 10% (1-2mg absorbed)
↑↑ Iron deficiency Anaemia, Growing children

59. Smita Pakhmode
• Heme:
– Hb , Myoglobin, Cytochromes,
Tryptophan Pyrrolase ,
catalase,peroxidase
• Fe-S:
– complex III Fe-S, succinate DH,
Xanthine Oxidase
• Non-heme iron:
Ferritin, Transferrin, Hemosiderin
IRON CONTAINING PROTEINS:

60. Smita Pakhmode
Functions of Iron:
• Hb /Myoglobin: Transport of O2 & CO2
•Cytochrome: ETC & Detoxification
•Peroxidase: Present in Lysosome, catalyzes
phagocytosis of bacteria by neutrophils.
• Immunocompetence of the body

61. Smita Pakhmode
SOURCES-
• Rich source: Organ Meat( Liver,heart & Kidney)
• Good source: Leafy Vegs., Pulses ,Cereals, ,
Jaggery, fish ,Apples,Dried fruits
• Poor source: Milk, wheat , polished rice
• Absorption-
• Upper duodenum & Proximal Jejunum
Fe2+
Fe3+
Ferroxidase/Ceruloplasmin
Ferroreductase
Transport form
Storage form

62. Smita Pakhmode

63. Smita Pakhmode
• ↑↑ by -
• HCL,
• Ascorbic acid, Cysteine, -SH gps of
proteins
• Iron deficiency Anaema(10 Times )
• ↓↓ by- Phytic acid (cereals)
Oxalic acid(vegetable), PO4
Alkaline pH
Malabsorption disorders(steatorrhoea)
Total or Partial Gastrectomy
Diet:
Fe3+ + Oragnic
acids/Pr.
HCl
Fe3+
Vit C, Cyst
Fe2+
Factors affecting Absorption of Iron:

64. Smita Pakhmode
GIT Lumen
Diet:
Mucosal cell Blood
Fe3+ + Oragnic
acids/Pr.
HCl
Fe3+
Vit C, Cyst
Fe2+
DMT Fe2+
Fe3+
Ferroxidase
Apoferritin
Mucosal
Ferritin
Fe3+
Ferrireductase
Ferroportin
Fe2+
Fe3+
Ferroxidase
Ceruloplasmin
Apotransferrin
Plasma (Fe3+)
Transferrin
Heme Pr.
Hb, My,
Cyt
Ferritin
Fe3+
Hemosiderin
Hepcidin
Liver, spleen, BM
Absorption storage and utilization of food Iron.
DMT= Divalent Metal transporter
Mucosal block theory for the
regulation of iron absorption
↑↑Ferritin

65. Smita Pakhmode
Total iron binding capacity
• Transferrin: Glycoprotein
• 1mol Of Transferrin-2 atoms of Fe3+
• N TIBC Plasma: 250mg/dl-400 mg of Iron/dl
• Normal condition 1/3 of transferrin is
saturated
• TIBC grossly increased in Iron deficiency
Anaemia.

66. Smita Pakhmode
• Ferritin:
• In liver , spleen, BM( as ferritin)
• (Apo-ferritin has 24 subunits (MW5,00,000)
• Can take up 4,500 Iron atoms/ molecules to
become ferritin
• Ferritin: 25% Iron by weight.
• In Iron toxicity , ferritin Increased is seen in plasma
IRON STORAGE(Permanent)
Hemosiderin:
35% of iron by its weight.
Accumulate in liver, spleen whenever there is excess of
demand of iron.

67. Smita Pakhmode
Iron is one way compound
• Once entered in the body, can not be excreted.
• It acts in close circuit.
• Utilized & reutilized
• Not excreted in urine
• < 1mg/day excreted through bile salt, sweat.
• It gets deposited in the body in form Hemosiderin.
Iron loss
Feces: Major loss of unabsorbed iron
Menstruating women (up to menopause)- 25-30 mg /day
Skin →cells lost

68. Smita Pakhmode
Iron is reutilized
RBC Lysis
Globin removed
HB: HB- Haptoglobin complex taken up by
liver kuffers cells
Iron
reutilized
Heme: Heme Hemopexin complex
Taken up by hepatocyte
Porphyrin ring opened. Bilirubin
Iron. → Iron transferrin → storage.
Iron
reutilized
Iron
reutilized
Renal insufficiency leads to iron
deficiency due to loss of
haptoglobin, hemopexin &
deficiency of erythropoietin

69. Smita Pakhmode
• Most common nutritional deficiency disorder
• 30% world population
• 85% pregnant women
• 15 % maternal deaths
• In children → irreversible impairment in
learning ability
IRON DEFICIENCY ANAEMIA

70. Smita Pakhmode
Iron deficiency Anaemia
Causes:
• Hookworm infestation
• Iron deficiency in diet
• Repeated pregnancy (1gm/delivery)
• Chr. Bloods loss ( piles/ Uterine hemorrhage)
• Renal defect (loss in urine)
• Lack of abs ( Subtotal gastrectomy, achlorhydria)
• Symptoms:
• “Microcytic Hypochromic Anaemia” (< 12gm/dl)
• Apathy, sluggish,
• atrophy of gastric epithelium
↓abs of iron achlorhydria
• Chronic deficiency → impaired attention /irritability
↓memory
poor school performance

71. Smita Pakhmode
TREATMENT
• 100 mg iron + 500 µg Folic Acid - Preg women
• 20 mg iron + 100 µg FA - children
IRON TOXICITY
• Haemosiderosis
Haemosiderin→ golden brown granules
↓ (spleen, liver)
Complexes of partially
denatured ferritin ( 25% iron)

72. Smita Pakhmode
1)Primary Haemosiderosis
• Abnormal gene on chr 6 (short arm)
• ↑abs of iron
• Excess iron deposit
2) Secondary Haemosiderosis
• Secondary to repeated blood transfusions
(hemophilia)
• Bantu tribes (Africa)
Iron vessels + low PO4 ( corn-staple diet)

73. Smita Pakhmode
Hemochromatosis:-
Direct iron deposition in tissues
Cirrhosis – liver
Diabetes – Pancreas
Yellow Brown Skin – Skin :
Bronze Diabetes
Treatment :
Repeated Phlebotomy + Desferrioxamins

74. Smita Pakhmode

75. Smita Pakhmode
COPPER(CU)….100MG
Plasma Cu
100-200 mg/dl
95% 5%
Ceruloplasmin Albumin
25-50 mg/dl 0.34% Cu
95% in RBCs as
colourless erythrocuprein
Rest as Ceruloplasmin in plasma
(serum ferroxidaseII )

76. Smita Pakhmode
RDA Sources
1.5- 3
mg/day
Cereals, nuts,
Meat , Liver, Kidney,
egg yolk,
Green leafy vegetables
(Milk poor source )
Absorption
Duodenum
Metallothionein pr facilitates abs
Phytate,Zinc,& Mo

77. Smita Pakhmode
Biochemical Function of Copper
Tyrosinase, uricase, catalase,
cytochrome oxidase, Monoamine oxidase,
Superoxide dismutase, ascorbic acid oxidase, phenol
oxidase,
• Essential constituent Enzymes:
•ALA synthase: For Hb synthesis
•Lysyl oxidase : cross linking of collagen & elastin
•Ceruloplasmin (Ferroxidase) : Fe+2 to Fe+3 –
(Transferrin) transported in plasma
•Tyrosinase:
• Synthesis of Melanin & phospholipids
• For Bone& nervous system(melanin) dev.

78. Smita Pakhmode
• Fe Absorption and incorporation into Hb
• Co factor for Vit C in hydroxylation reaction
• Component of Cu containing non enzymatic proteins e.g.
Hepatocuprein,
Cerebrocuprein
Hemocuprein
Biochemical Function of Copper

79. Smita Pakhmode
Deficiency :
-Microcytic Normochromic Anaemia
-Weakening of walls of major vessels-
fragility of arteries
-demineralization of bones, demyelination of neural
tissue, myocardial fibrosis,
-Hypopigmentation ( tyrosinase)
Greying of hair

80. Smita Pakhmode
Deficiency of Cu: Menke’s disease

81. Smita Pakhmode
Menke’s disease :
-X linked disorder
• Cu is absorbed by intestine but can not be transported to
blood.
• Absence of intracellular copper binding ATPase.
• Cu may be trapped by metallothionein in the intestinal
cells
• Not mobilized to other tissues.
S/S
decreased Cu in plasma & urine
Anemia,
De pigmentation of hair
Kinky ,twisted brittle hair( Cu catalyzed S-S bond formation)
Seizurs & Metal retardation

82. Smita Pakhmode
Wilson’s disease
Defective ATP 7A gene:
Cu Binding ATPase
↓Excretion of Cu through intestine from bile
↑ Absorption of Cu from Kidney
↓hepatic incorporation of copper in ceruloplsmin
Free Cu accumulates in the organs
Liver
Hepatic cirrhosis
Brain
necrosis
Renal damage:
↑excertion of AA,
Glu,peptide & Hb.
( hepatolenticular degeneration)
AR, 1:5000

83. Smita Pakhmode
Symptoms of Wilson’s disease
Hepatolenticular degeneration

84. Smita Pakhmode
Treatment
• diet low in copper
•Penicillamine -Cu chelating
agent
↓
excretion of cu in urine

85. Smita Pakhmode
Copper toxicity
• Diarrohea
• Blue green saliva
• Hemolysis
• Hb-uria
• Proteinuria
• Kidney failure

86. Smita Pakhmode
Case study
• A 13 year old boy reported with jaundice, fatigue,
muscle stiffness, tremors and behavioural changes.
Examination revealed an enlarged liver and spleen,
Kayser – ring noted.
• i) What is the probable diagnosis?
• Wilson’s Disease(Hepatolenticular degenerations)
• ii) Which organs are affected?
• Liver, CNS, Spleen, Eye.
• iii) What are the causes for the disease?
• Increased accumulation Cu in above organs leading
Hepatic Cirrhosis and Cerebral necrosis.
• iv) What is the treatment suggested
• Low copper diet & D Penicillamine(Chelating agent)

87. Smita Pakhmode
Case Study:
A Patient in the hospital had seizures and usually
appear weak and tired. Physical finding was
deposition of copper in eyes as green ring round
the cornea and hepatomegaly
• i) What is probable disease?
• ii) What is biochemical problem in this disease?
• iii) What is treatment to this disease?
• iv) Name any four copper containing enzymes.

88. Smita Pakhmode
FLUORINE
• Sources: drinking water
Req:<2 ppm
(one part of fluorine:in one million parts of
drinking water)
Should not exceed 3ppm

89. Smita Pakhmode
Functions
• prevent dental caries:
fluoroapatite with hydroxyapatite of
enamel forms protective covering.
↓ bacterial enzymes ⇢↓ production of acids
• normal bone development
• Enzyme Inhibitors:
Sodium fluoride- enolase(glycolysis)
Fluoroacetate - aconitase(TCA)

90. Smita Pakhmode
Disease States
• Dental Caries: (<0.5 ppm)
• T/t: Flouridation of Water
• Use of flouride toothpaste
• Fluoride toxicity –
• Dental Fluorosis :(>2ppm,particularly >5 ppm)
mottling of enamel, discoloration of teeth
Weak, rough, brown yellow patches
•

91. Smita Pakhmode
Skeletal Fluorosis(>20 ppm)
Hypercalcification of Bone & Ligaments
Joint stiffness and Bone density.
Neurological disturbances
Advanced Flurosis:
Stiff Joints crippling state- genu valgum

92. Smita Pakhmode
IODINE
• -
Sources:
Salts(Iodine fortified), Sea foods, drinking water, vegetables,
fruits.
High altitudes:
areas deficient in iodine content in water as well as
soil
Iodine is added to drinking water or to table salt in
these regions
TOTAL BODY
CONTENT- 20 mg
80% Thyroglobulin
20%Muscle , salivary
glands, ovaries

93. Smita Pakhmode
Dietary retirements
Adults: _100-150 ug/day
Pregnant woman – 200 ug/day

94. Smita Pakhmode
Synthesis of Thyroid Hormone
• Synthesis of thyroglobulin precursor:
• Tg Glycoprotein, Dimer. Synthesized in follicular cells of glands
• Iodine uptake by gland.
• Uptake from blood, active process, needs Na-K pump
• Follicular cell I2 content > then Blood
• Iodination of Thyroid residue:
• Formation of mature TG(organification of Iodine)
• Peroxidase enz. Imp
• Coupling:
• MIT + DIT = T3
• DIT + DIT = T4
• Hydrolysis of thyroglobulin: To release Thyroid precursor
• Secretion & transport of T4 & T3: Free form < Bound with Alb & TBG
• Peripheral conversion of T4 to T3:
• Enzyme deiodinase
• T4 T3

95. Smita Pakhmode
Synthesis of Thyroid hormone

96. Smita Pakhmode
Regulation of thyroid Hormone

97. Smita Pakhmode
Functions of Thyroid glands
• Development of CNS
• Regulation of Normal body growth:
Promote general body growth
Calcification of Bone
• Regulations of BMR
• Regulations of fuel Metabolism:
Amplifiers of cellular metaboilic activity
Increase uptake of LDL Cholesterol
Actions are opposite to the insulin

98. Smita Pakhmode
Function
• Synthesis of thyroid hormones
• Thyroxine(T4) ,Triiodothyronine(T3)
plasma iodine – 4-10 mg/dl
Bound with PBI(Plasma Bound
Iodine
Disease states
Simple goiter
Toxic goiter

99. Smita Pakhmode
Zinc
RDA Sources Absorption Blood levels
10-
15mg/day
Grains, beans
nuts, cheese,
Meat, fish, eggs,
milk etc
duodenum (by phytates , Ca, Cu,
Fe)
Stored in liver (metallothionein)
excretion via Pancreatic juice and
sweat
100mg/dl
TB : 2 gm
Prostate gland –very rich(100mg/g)

100. Smita Pakhmode
Functions
• More than 300 enzymes
Carboxypeptidase , CA, Alk. Phos, , Ethanol DH,
SOD , RNA Polymerase
• Maintains level of Vit A:Retinol BP Synthesis
• Wound healing
• ↑cell growth, division,stabilizes membrane
• Reproduction
• Immunological function
• Storage & secretion of insulin in  cells of pancreas
• Gusten ( saliva) - taste sensation

101. Smita Pakhmode
Zinc Deficiency
( Chronic Alcoholism )
•Growth retardation
•Poor wound healing
•Skin lesions
•( hyperkeratosis , alopecia , dermitis )
•Depression
•Dementia
•Loss of appetite
•Loss of taste sensation,
•Impaired spermatogenesis
•anemia

102. Smita Pakhmode
Acrodermatitis enteropathica
Rare inherited metabolic disease of Zn deficiency
Defect in the absorption of zinc from intestine
• Inflammation around mouth nose & fingers
• Diarrhea
• Alopecia
• Hypogonadism
Zinc Toxicity
Acute - ( Welder’s fumes- Zn oxide)
Excess salivation , Fever , headache ,Leucocytosis
Chronic – Gastric ulcer , Pancreatitis , Anemia ,
Nausea, Pulmonary fibrosis

103. Smita Pakhmode
SELENIUM
• Soil content
• Requirement : 50-200 µg / day
• Sources- organ meats , sea foods
Antioxidant Mineral
Acts with Vitamin E

104. Smita Pakhmode
Functions
With vit E prevents hepatic necrosis & muscular dystrophy
Maintain structural integrity
Lipid peroxidation
Heavy metals(Hg, Cd)
Selenocystiene -Glutathione peroxidase - Antioxidant enzyme
5’deiodinase [ T4 →T3 ]
Thioredoxin reductase(purine meta) is a selenoprotein

105. Smita Pakhmode
• KESHAN DISEASE ( China)
Soil deficient in selenium
Endemic cardiomyopathy
• Cardiovascular disease & various cancer
Toxicity
SELENOSIS
900 mg/ day ( Metal Polishes , antirust)
hair loss , falling nails ,emotional disturbances,
diarrhea, weight loss
garlic odor in breath ( dimethyl selenide)

106. Smita Pakhmode
Manganese(Mn)
Functions
• Cofactor –arginase, puruvate carboxylase,
isocitrate dehydrogenase, SOD & peptidase
• Bone development, reproduction, Normal
functioning of nervous system
• Hb synthesis
• Inhibits lipid peroxidation
• Cholesterol biosynthesis

107. Smita Pakhmode
Disease states
In animals
• Retarded growth, bone deformities, sterility
• Accumulation of fat in liver
• Increased activity of serum alkaline
phosphatase
• Diminished activity of B-cells of pancrease

108. Smita Pakhmode
MOLYBDENUM
xanthine oxidase,
Requirement not clearly known
Widely distributed in natural foods
Molybdenosis

109. Smita Pakhmode
Cobalt
• Constituent of vitamin B12
• Stimulates production of erythropoietin
• Prolonged administration leads to
polycythemia

110. Smita Pakhmode
Chromium
TB – 6 mg
• utilization of glucose with insulin
• Component of protein chromodulin
• binding of insulin to cell receptor sites
• lipoprotein metabolism
• Decreases LDL & increases HDL
• Transport of AA into the cells
• Yeast, grains, cereals, cheese & meat
• Deficiency- carbohydrate , lipid, protein metabolism
• Toxicity- liver & kidney damage

111. Smita Pakhmode
Commonly asked questions for MBBS
Commonly asked questions in university exams
• Sources, RDA ,disease manifestation of iron
(8m)
• Absorption of iron (4m)
• Iron toxicity (4m)
• Heme containing protein (4m)

112. Smita Pakhmode
References:
Text book of biochemistry Vasudevan: 9th
Edition
Text book of biochemistry by Pankaja Naik:
5th Edition
Text book of biochemistry by Rafi: 4th
Edition
Biochemistry by Satyanarayana
Harpers Biochemistry

113. Smita Pakhmode
113
Dr. Smita Pakhmode
Asso. Prof. Biochemistry.
NKP SIMS & RC, Nagpur